DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Relatório |
Idioma: | eng |
Título da fonte: | Genetics and Molecular Biology |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572015000200147 |
Resumo: | Centronuclear myopathy (CNM) is a rare congenital muscle disease characterized by fibers with prominent centralized nuclei in muscle biopsies. The disease is clinically heterogeneous, ranging from severe neonatal hypotonic phenotypes to adult-onset mild muscle weakness, and can have multiple modes of inheritance in association with various genes, including MTM1, DNM2, BIN1 and RYR1. Here we analyzed 18 sporadic patients with clinical and histological diagnosis of CNM and sequenced the DNM2 gene, which codes for the dynamin 2 protein. We found DNM2 missense mutations in two patients, both in exon 8, one known (p.E368K) and one novel (p.F372C), which is found in a position of presumed pathogenicity and appeared de novo. The patients had similar phenotypes characterized by neonatal signs followed by improvement and late childhood reemergence of slowly progressive generalized muscle weakness, elongated face with ptosis and ophthalmoparesis, and histology showing fibers with radiating sarcoplasmic strands (RSS). These patients were the only ones in the series to present this histological marker, which together with previous reports in the literature suggest that, when RSS are present, direct sequencing of DNM2 mutation hot spot regions should be the first step in the molecular diagnosis of CNM, even in sporadic cases. |
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DNM2 mutations in a cohort of sporadic patients with centronuclear myopathycentronuclear myopathyDNM2dynamin 2congenital myopathyCentronuclear myopathy (CNM) is a rare congenital muscle disease characterized by fibers with prominent centralized nuclei in muscle biopsies. The disease is clinically heterogeneous, ranging from severe neonatal hypotonic phenotypes to adult-onset mild muscle weakness, and can have multiple modes of inheritance in association with various genes, including MTM1, DNM2, BIN1 and RYR1. Here we analyzed 18 sporadic patients with clinical and histological diagnosis of CNM and sequenced the DNM2 gene, which codes for the dynamin 2 protein. We found DNM2 missense mutations in two patients, both in exon 8, one known (p.E368K) and one novel (p.F372C), which is found in a position of presumed pathogenicity and appeared de novo. The patients had similar phenotypes characterized by neonatal signs followed by improvement and late childhood reemergence of slowly progressive generalized muscle weakness, elongated face with ptosis and ophthalmoparesis, and histology showing fibers with radiating sarcoplasmic strands (RSS). These patients were the only ones in the series to present this histological marker, which together with previous reports in the literature suggest that, when RSS are present, direct sequencing of DNM2 mutation hot spot regions should be the first step in the molecular diagnosis of CNM, even in sporadic cases.Sociedade Brasileira de Genética2015-06-01info:eu-repo/semantics/reportinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572015000200147Genetics and Molecular Biology v.38 n.2 2015reponame:Genetics and Molecular Biologyinstname:Sociedade Brasileira de Genética (SBG)instacron:SBG10.1590/S1415-4757382220140238info:eu-repo/semantics/openAccessAbath Neto,OsorioMartins,Cristiane de AraújoCarvalho,MaryChadi,GersonSeitz,Katia WerneckOliveira,Acary Souza BulleReed,Umbertina ContiLaporte,JocelynZanoteli,Edmareng2015-07-31T00:00:00Zoai:scielo:S1415-47572015000200147Revistahttp://www.gmb.org.br/ONGhttps://old.scielo.br/oai/scielo-oai.php||editor@gmb.org.br1678-46851415-4757opendoar:2015-07-31T00:00Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG)false |
dc.title.none.fl_str_mv |
DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy |
title |
DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy |
spellingShingle |
DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy Abath Neto,Osorio centronuclear myopathy DNM2 dynamin 2 congenital myopathy |
title_short |
DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy |
title_full |
DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy |
title_fullStr |
DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy |
title_full_unstemmed |
DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy |
title_sort |
DNM2 mutations in a cohort of sporadic patients with centronuclear myopathy |
author |
Abath Neto,Osorio |
author_facet |
Abath Neto,Osorio Martins,Cristiane de Araújo Carvalho,Mary Chadi,Gerson Seitz,Katia Werneck Oliveira,Acary Souza Bulle Reed,Umbertina Conti Laporte,Jocelyn Zanoteli,Edmar |
author_role |
author |
author2 |
Martins,Cristiane de Araújo Carvalho,Mary Chadi,Gerson Seitz,Katia Werneck Oliveira,Acary Souza Bulle Reed,Umbertina Conti Laporte,Jocelyn Zanoteli,Edmar |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Abath Neto,Osorio Martins,Cristiane de Araújo Carvalho,Mary Chadi,Gerson Seitz,Katia Werneck Oliveira,Acary Souza Bulle Reed,Umbertina Conti Laporte,Jocelyn Zanoteli,Edmar |
dc.subject.por.fl_str_mv |
centronuclear myopathy DNM2 dynamin 2 congenital myopathy |
topic |
centronuclear myopathy DNM2 dynamin 2 congenital myopathy |
description |
Centronuclear myopathy (CNM) is a rare congenital muscle disease characterized by fibers with prominent centralized nuclei in muscle biopsies. The disease is clinically heterogeneous, ranging from severe neonatal hypotonic phenotypes to adult-onset mild muscle weakness, and can have multiple modes of inheritance in association with various genes, including MTM1, DNM2, BIN1 and RYR1. Here we analyzed 18 sporadic patients with clinical and histological diagnosis of CNM and sequenced the DNM2 gene, which codes for the dynamin 2 protein. We found DNM2 missense mutations in two patients, both in exon 8, one known (p.E368K) and one novel (p.F372C), which is found in a position of presumed pathogenicity and appeared de novo. The patients had similar phenotypes characterized by neonatal signs followed by improvement and late childhood reemergence of slowly progressive generalized muscle weakness, elongated face with ptosis and ophthalmoparesis, and histology showing fibers with radiating sarcoplasmic strands (RSS). These patients were the only ones in the series to present this histological marker, which together with previous reports in the literature suggest that, when RSS are present, direct sequencing of DNM2 mutation hot spot regions should be the first step in the molecular diagnosis of CNM, even in sporadic cases. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-06-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/report |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
report |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572015000200147 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572015000200147 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/S1415-4757382220140238 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Genética |
publisher.none.fl_str_mv |
Sociedade Brasileira de Genética |
dc.source.none.fl_str_mv |
Genetics and Molecular Biology v.38 n.2 2015 reponame:Genetics and Molecular Biology instname:Sociedade Brasileira de Genética (SBG) instacron:SBG |
instname_str |
Sociedade Brasileira de Genética (SBG) |
instacron_str |
SBG |
institution |
SBG |
reponame_str |
Genetics and Molecular Biology |
collection |
Genetics and Molecular Biology |
repository.name.fl_str_mv |
Genetics and Molecular Biology - Sociedade Brasileira de Genética (SBG) |
repository.mail.fl_str_mv |
||editor@gmb.org.br |
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1752122386284544000 |